TY - JOUR

T1 - In vitro- and in vivo-produced male dairy calves show molecular differences in the hepatic and muscular energy regulation(dagger)

AU - Rabaglino, Maria B.

AU - Secher, Jan Bojsen-Moller

AU - Hyttel, Poul

AU - Kadarmideen, Haja N.

PY - 2022

Y1 - 2022

N2 - In cattle, the in vitro production (IVP) of embryos is becoming more relevant than embryos produced in vivo, i.e. after multiple ovulation and embryo transfer (MOET). However, the effects of IVP on the developmental programming of specific organs in the postnatal calves are yet unknown. Previously, we reported an epigenomic and transcriptomic profile of the hypothalamus-pituitary-testicular axis compatible with its earlier activation in IVP calves compared to MOET animals. Here, we studied the hepatic and muscular epigenome and transcriptome of those same male dairy calves (n = 4 per group). Tissue samples from liver and semitendinosus muscle were obtained at 3 months of age, and the extracted gDNA and RNA were sequenced through whole-genome bisulfite sequencing and RNA-sequencing, respectively. Next, bioinformatic analyses determined differentially methylated cytosines or differentially expressed genes [false discovery rate (FDR) < 0.05] for each Omic dataset; and nonparametrically combined genes (NPCG) for both integrated omics (P < 0.05). KEGG pathways enrichment analysis showed that NPCG upregulated in the liver and the muscle of the IVP calves were involved in oxidative phosphorylation and the tricarboxylic acid cycle. In contrast, ribosome and translation were upregulated in the liver but downregulated in the muscle of the IVP calves compared to the MOET calves (FDR < 0.05). A model considering the effect of the methylation levels and the group on the expression of all the genes involved in these pathways confirmed these findings. In conclusion, the multiomics data integration approach indicated an altered hepatic and muscular energy regulation in phenotypically normal IVP calves compared to MOET calves.Transcriptomic and epigenomic results suggest that aerobic respiration was upregulated in both liver and muscle, while protein synthesis was increased in the liver but downregulated in the muscle of in vitro produced calves compared to in vivo counterparts.

AB - In cattle, the in vitro production (IVP) of embryos is becoming more relevant than embryos produced in vivo, i.e. after multiple ovulation and embryo transfer (MOET). However, the effects of IVP on the developmental programming of specific organs in the postnatal calves are yet unknown. Previously, we reported an epigenomic and transcriptomic profile of the hypothalamus-pituitary-testicular axis compatible with its earlier activation in IVP calves compared to MOET animals. Here, we studied the hepatic and muscular epigenome and transcriptome of those same male dairy calves (n = 4 per group). Tissue samples from liver and semitendinosus muscle were obtained at 3 months of age, and the extracted gDNA and RNA were sequenced through whole-genome bisulfite sequencing and RNA-sequencing, respectively. Next, bioinformatic analyses determined differentially methylated cytosines or differentially expressed genes [false discovery rate (FDR) < 0.05] for each Omic dataset; and nonparametrically combined genes (NPCG) for both integrated omics (P < 0.05). KEGG pathways enrichment analysis showed that NPCG upregulated in the liver and the muscle of the IVP calves were involved in oxidative phosphorylation and the tricarboxylic acid cycle. In contrast, ribosome and translation were upregulated in the liver but downregulated in the muscle of the IVP calves compared to the MOET calves (FDR < 0.05). A model considering the effect of the methylation levels and the group on the expression of all the genes involved in these pathways confirmed these findings. In conclusion, the multiomics data integration approach indicated an altered hepatic and muscular energy regulation in phenotypically normal IVP calves compared to MOET calves.Transcriptomic and epigenomic results suggest that aerobic respiration was upregulated in both liver and muscle, while protein synthesis was increased in the liver but downregulated in the muscle of in vitro produced calves compared to in vivo counterparts.

KW - bioinformatics

KW - system biology

KW - multi-omics

KW - fetal programming

KW - IN-VITRO

KW - REPRODUCTIVE TECHNOLOGIES

KW - PLACENTAL INSUFFICIENCY

KW - GENE-EXPRESSION

KW - EARLY-PREGNANCY

KW - EMBRYO CULTURE

KW - GROWTH

KW - FERTILIZATION

KW - CONSEQUENCES

KW - TRANSLATION

U2 - 10.1093/biolre/ioac131

DO - 10.1093/biolre/ioac131

M3 - Journal article

C2 - 35766406

VL - 107

SP - 1113

EP - 1124

JO - Biology of Reproduction

JF - Biology of Reproduction

SN - 0006-3363

IS - 4

ER -